The field of present invention is novel antibiotic BU-4641V having antibacterial, anti-tumor (anti-cancer) and antiviral activities.
Acquired immunodeficiency syndrome (AIDS) is an infectious disease characterized by severe impairment of the cell-mediated immune system in the patient. Recent epidemiological and molecular biochemical research results evidently indicate that human immunodeficiency virus (HIV) is the major etiological agent of AIDS. Many anti-HIV agents have been reported such as antibodies to the virus or cellular receptors, sulphated polysaccharides having an ability to block adsorption of virions to target cells, 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-dideoxycytidine (DDC) and tetrahydro-imidazo-[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) for inhibiting a reverse transcriptase-associated process (R. Pauwels, et al., Potent and selective inhibition of HIV-I replication in vitro by a novel series of TIBO derivatives, Nature, 343, pp 470-474, 1990), synthetic peptides for inhibiting viral protease (C. Debouck & B. W. Metcalf, Human immunodeficiency virus protease: a target for AIDS therapy, Drug Development Research, 21, pp 1-17, 1990), and castanospermine for inhibiting myristoylation and glycosylation of virions (See review of: H. Mitsuya, R. Yarchoan & S. Broder, Molecular targets for AIDS therapy, Science, 249, pp 1533-1544, 1990).
The HIV envelope glycoprotein, gp-160, is essential for the viral entry into cells. The gp-120 expressed on HIV-infected cells interact with the CD4 surface antigen on target cells. This interaction precedes a post-binding fusion event mediated by the HIV transmembrane gp-41, leading to a multinucleated giant cell called syncytium. As described above, the sulphated poly-saccharides such as dextran sulphate clearly inhibit this syncytium formation, and consequently the in vitro HIV infection. From this point of view, syncytium formation inhibitors are potential anti-HIV agents. We have now isolated, from fermentation broths of Arthrinium sp. FA1744, BU-4641V with heretofore unknown structure and with stronger syncytium inhibitory property than that of dextran sulfate.
Further, BU-4641V has been found to promote tubulin polymerization, a property which confers taxol, a well-known anticancer drug, its anti-tumor ability. Thus, BU-4641V has anti-tumor properties. Additionally, BU-4641V was also found to have anti-bacterial properties.